Biomod/2012/Harvard/BioDesign
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Into the Mirror World: Using an information-rich but nuclease-sensitive self-assembled D-DNA scaffold to template an information-poor but nuclease-resistant L-DNA nano-structure
Abstract:
It is now possible to create fully-addressable nanostructures from hundreds of unique synthetic DNA strands. Such structures, being made of biologically-natural D-DNA, are easily degraded by nucleases, posing a potential problem for in-vivo applications such as drug delivery. The oppositely-chiral L-DNA cannot be so degraded due to the inability of chiral nucleases to recognize and attack its mirror-image structure. Unfortunately, L-DNA is currently much more expensive than D-DNA. Here we demonstrate a method for inexpensively creating L-DNA structures with controlled shapes: a repetitive L-DNA structure is templated on an inexpensive, all-unique D-DNA layer. The D-DNA layer forms first, exposing D-DNA handles at defined locations. Subsequently, alternating rows of identical L-DNA/D-DNA chimerical strands are added through hybridization of complementary handles. The D-DNA template can then be enzymatically degraded while the assembled L-DNA structure stays intact, resulting in an economical yet nuclease-resistant nanostructure.
